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| 1 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 2 | Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-1igase signaling effector DWARF3显示文摘 | Li-Hua Zhao X Edward Zhou Wei Yi Zhongshan Wu Yue Liu Yanyong Kang Li Hou Parker W de Waal Suling Li Yi Jiang Adrian Scaffidi Gavin R Flematti Steven M Smith Vinh Q Lam Patrick R Griffin YonghongWang Jiayang Li Karsten Melcher H Eric Xu | 2015 | Cell Research2015，25，11： | 7 |
| 3 | Neonatal vitamin A injection promotes cattle muscle growth and increases oxidative muscle fibers显示文摘Background: Vitamin A and its metabolite,retinoic acid(RA),are important regulators of cell differentiation and organ morphogenesis.Its impact on beef cattle muscle growth remains undefined.Method: Angus steer calves were administrated with 0(control) or 150,000 IU vitamin A(retinyl palmitate in glycerol,i.m.) per calf at birth and 1 month of age.At 2 months of age,a biopsy of the Biceps femoris muscle was obtained to analyze the immediate effects of vitamin A injection on myogenic capacity of muscle cells.The resulting steers were harvested at 14 months of age.Results: Vitamin A administration increased cattle growth at 2 months.At 2 months of age,Vitamin A increased PAX7 positive satellite cells and the expression of myogenic marker genes including PAX7,MYF5,MYOD and MYOG.Muscle derived mononuclear cells were further isolated and induced myogenesis in vitro.More myotubes and a higher degree of myogenesis was observed in vitamin A groups.Consistently,vitamin A increased Latissimus dorsi(LD) muscle fiber size at harvest.In addition,vitamin A increased the ratio of oxidative type I and type IIA fibers and reduced the glycolic type IIX fibers.Furthermore,we found that RA,a key bioactive metabolite of vitamin A,activated PPARGC1 A promoter,which explains the upregulated expression of PPARGC1 A in skeletal muscle.Conclusion: Vitamin A administration to neonatal calves enhanced postnatal muscle growth by promoting myogenesis and increasing satellite cell density,accompanied with a shift to oxidative muscle fibers. | Bo Wang Wei Nie Xing Fu Jeanene M de Avila Yannan Ma Mei-Jun Zhu Martin Maquivar Steven M Parish Jan R Busboom Mark L Nelson Min Du | 2019 | Journal of Animal Science and Biotechnology2019，10，1： | 3 |
| 4 | Cholangiocarcinoma, gone without the Wnt?显示文摘Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy. | Anne T R Noll Thorsten Cramer Steven W M Olde Damink Frank G Schaap | 2016 | World Journal of Hepatology2016，8，26： | 3 |
| 5 | Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma显示文摘This report describes a patient that developed recurrent metastatic hepatocellular carcinoma(HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. | Michael L Caparelli Nathan J Roberts Timothy S Braverman Robert M Stevens Edward R Broun Shyam Allamaneni | 2016 | World Journal of Hepatology2016，8，23： | 2 |
| 6 | Inflammation and Alzheimer’s disease显示文摘 | Haruhiko Akiyama Steven Barger Scott Barnum Bonnie Bradt Joachim Bauer Greg M Cole Neil R Cooper Piet Eikelenboom Mark Emmerling Berndt L Fiebich Caleb E Finch Sally Frautschy W.S.T Griffin Harald Hampel Michael Hull Gary Landreth Lih–Fen Lue Robert Mrak | 2000 | Neurobiology of Aging2000，，3： | 2 |
| 7 | Soil moisture: A central and unifying theme in physical geography显示文摘 | Legates David R Mahmood Rezaul Levia Delphis F DeLiberty Tracy L Quiring Steven M Houser Chris Nelson Frederick E | 2011 | Progress in Physical Geography2011，，1： | 2 |
| 8 | Complete genomes of two clinical Staphylococcus aureus strains:evidence for the rapid evolution of virulence and drug resistance显示文摘 | Holden MT Feil EJ Lindsay JA Peacock SJ Day NP Enright MC Foster TJ Moore CE Hurst L Atkin R Barron A Bason N Bentley SD Chillingworth C Chillingworth T Churcher C Clark L Corton C Cronin A Doggett J Dowd L Feltwell T Hance Z Harris B Hauser H Holroyd S Jagels K James KD Lennard N Line A Mayes R Moule S Mungall K Ormond D Quail MA Rabbinowitsch E Rutherford K Sanders M Sharp S Simmonds M Stevens K Whitehead S Barrell BG Spratt BG Parkhill J | 2004 | Proc Natl Acad Sci USA2004，101，26： | 1 |
| 9 | Heavy metal assessment for surface sediments fromthree areas of the Portuguese continental shelf 显示文摘 | Mil-Homens M Stevens R L Abrantes F | 2006 | Continental Shelf Research2006，26，10： | 1 |
| 10 | Synthetic aperture imaging laser radar laboratory demonstration and signal processing显示文摘 | Steven M B and Jiseph R B | 2005 | Applied Optics2005，44，35： | 1 |
| 11 | Gatlin Ⅲ Growth and body composition of juvenile red drum (Sciaenops ocellatus) fed diets containing lecithinand supplemental choline显示文摘 | Steven R Craig Delbert M | 1997 | Aquaculture1997，151，： | 1 |
| 12 | Use of buffeting and other means to improve results of problem atic pesticides in a fast and easy method for residue analysis of fruits and vegetables 显示文摘 | STEVEN J L KATEIINA M ALAN R L | 2005 | JAOAC Int2005，88，2： | 1 |
| 13 | Properties of skeletal muscle mitochondria isolated from subsarcolemmal and intermyofibrillar regions 显示文摘 | Cogswell A M Stevens R J Hood D A | 1993 | American Journal Physiology-Cell Physiology1993，264，： | 1 |
| 14 | Cryogenic refrigerationsystem for HTS cables 显示文摘 | Lee R C Aly Dada Steven M | 2005 | IEEE Transactions on Ap-plied Superconductivity2005，15，2： | 1 |
| 15 | Structural basis for selective inhibition of cyclooxygenase- 2 by anti-inflammatory agents 显示文摘 | KURUMBAIL R G STEVENS A M GIERSE J K | 1996 | Nature1996，384，： | 1 |
| 16 | Processes leading to N2 O emissions in grassland soil during freezing and thawing 显示文摘 | Muller C Martin M Stevens R J | 2002 | Soil Biology and Biochemistry2002，34，9： | 1 |
| 17 | Network Firewalls显示文摘 | William R C | 1994 | IEEE Communications1994，，9： | 1 |
| 18 | Pattern of liver enzyme elevations in acute ST - elevation myocardial in- farction显示文摘 | LOFTHUS D M STEVENS S R ARMSTRONG P W | 2012 | Coron Artery Dis2012，23，1： | 1 |
| 19 | Influence of niobium and zirconium alloying additions on the anodic dissolution behavior of activated titanium in HCl solutions显示文摘 | STEVEN Y Y SCULLY J R VITUS C M | | 0，，02： | 1 |
| 20 | Horizon- tal structures of velocity and temperature boundary layers in two-dimensional numerical turbulent Rayleigh-Benard convection显示文摘 | Zhou Q Sugiyama K Stevens R J A M | | 0，，： | 1 |
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